Therefore, this study aimed to systematically validate the clinical significance of MYBL2, elucidate its functional role in tumor progression and drug sensitivity, and identify its upstream regulatory mechanisms using an integrative machine learning and experimental framework.<h4>Methods</h4>We applied an integrative pipeline combining LASSO-based feature selection on TCGA and GEO cohorts, single-cell transcriptomics, pharmacogenomic surveys, and CRISPR dependency screens. Here, MYBL2 is linked to neoplasm.